Assessing efficacy of different nucleos(t)ide backbones in NNRTI-containing regimens in the Swiss HIV Cohort Study.

Abstract

BACKGROUND:

The most recommended NRTI combinations as first-line antiretroviral treatment for HIV-1 infection in resource-rich settings are tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. Efficacy studies of these combinations also considering pill numbers, dosing frequencies and ethnicities are rare.

METHODS:

We included patients starting first-line combination ART (cART) with or switching from first-line cART without treatment failure to tenofovir/emtricitabine, abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine plus efavirenz or nevirapine. Cox proportional hazards regression was used to investigate the effect of the different NRTI combinations on two primary outcomes: virological failure (VF) and emergence of NRTI resistance. Additionally, we performed a pill burden analysis and adjusted the model for pill number and dosing frequency.

RESULTS:

Failure events per treated patient for the four NRTI combinations were as follows: 19/1858 (tenofovir/emtricitabine), 9/387 (abacavir/lamivudine), 11/344 (tenofovir/lamivudine) and 45/1244 (zidovudine/lamivudine). Compared with tenofovir/emtricitabine, abacavir/lamivudine had an adjusted HR for having VF of 2.01 (95% CI 0.86-4.55), tenofovir/lamivudine 2.89 (1.22-6.88) and zidovudine/lamivudine 2.28 (1.01-5.14), whereas for the emergence of NRTI resistance abacavir/lamivudine had an HR of 1.17 (0.11-12.2), tenofovir/lamivudine 11.3 (2.34-55.3) and zidovudine/lamivudine 4.02 (0.78-20.7). Differences among regimens disappeared when models were additionally adjusted for pill burden. However, non-white patients compared with white patients and higher pill number per day were associated with increased risks of VF and emergence of NRTI resistance: HR of non-white ethnicity for VF was 2.85 (1.64-4.96) and for NRTI resistance 3.54 (1.20-10.4); HR of pill burden for VF was 1.41 (1.01-1.96) and for NRTI resistance 1.72 (0.97-3.02).

CONCLUSIONS:

Although VF and emergence of resistance was very low in the population studied, tenofovir/emtricitabine appears to be superior to abacavir/lamivudine, tenofovir/lamivudine and zidovudine/lamivudine. However, it is unclear whether these differences are due to the substances as such or to an association of tenofovir/emtricitabine regimens with lower pill burden.

• Authors: Wan-Lin Yang, Roger D Kouyos, Alexandra U Scherrer, Jürg Böni, Cyril Shah, Sabine Yerly, Thomas Klimkait, Vincent Aubert, Cédric Hirzel, Manuel Battegay, Matthias Cavassini, Enos Bernasconi, Pietro Vernazza, Leonhard Held, Bruno Ledergerber, Huldrych F Günthard, Swiss HIV Cohort Study (SHCS), Swiss HIV Cohort Study SHCS
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 70 Issue 12 Pg. 3323-31 (Dec 2015) ISSN: 1460-2091 [Electronic] England
• PMID: 26362944 (Publication Type: Clinical Study, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Nucleosides
• Nucleotides
• Reverse Transcriptase Inhibitors

Topics

• Adult
• Antiretroviral Therapy, Highly Active (methods)
• Drug Resistance, Viral
• Female
• HIV Infections (drug therapy)
• HIV-1
• Humans
• Male
• Middle Aged
• Nucleosides (therapeutic use)
• Nucleotides (therapeutic use)
• Reverse Transcriptase Inhibitors (therapeutic use)
• Switzerland
• Treatment Failure